Background Substantial evidence supports the implication of immune-activated cells, cytokines and chemokines in the pathogenesis of systemic sclerosis (SSc). The frequency of T cells expressing activation markers is increased in the peripheral blood (PB) of SSc patients. Proinflammatory cytokines, such as IL-2, TNF-α and IFN-γ, seem to be mostly involved in immune responses at early stages of the disease. However, discrepancies exist between the results of several studies.
Objectives We undertook the present study to investigate the pattern of expression of proinflammatory cytokines by PB Th1 and Tc1 populations and to explore associations with disease duration.
Methods Forty SSc patients and 18 healthy controls (HC) were included. All SSc patients fulfilled the American College of Rheumatology Criteria for the classification of SSc (limited cutaneous SSc (lSSc, n=29) or diffuse cutaneous SSc (dSSc, n=11), according to LeRoy et al.). A further subdivision was made, based upon the duration of disease, as early- (n=11) and late-stage (n=30), and these groups were individually compared with HC. A thorough clinical evaluation was performed and registered. The autoantibody profile was collected from medical records.
All patients signed an informed consent and provided a PB sample, which was processed to separately analyze the intracellular expression of IL-2, TNF-α and IFN-γ in Th1 and Tc1 cell populations.
Data was statistically analyzed using the SPSS® version 20.0 for windows. Mann-Whitney and Kruskal-Wallis tests were used to evaluate differences between groups. Correlations between continuous variables were assessed by Spearman’s correlation coefficient. P values < 0.05 were considered statistically significant.
Results The mean age was 56.0±11.9 and 51.7±9.9 years for SSc patients and HC respectively. Females represented 77.5% of SSc and 83.3% of the control group. The mean disease duration was 9.6±8.55 years, the mean mRSS was 11.60±7.65 and the mean disease activity was 2.74±2.47.
The frequency of Th1 and Tc1 circulating cells was not statistically different between SSc patients and HC.
The percentage of Th1 and Tc1 cells producing TNF-α was significantly higher in late-stage than in early-stage SSc (p=0.034 and p=0.005, respectively). The percentage of Tc1 cells producing IFN-γ was significantly lower in early-stage than in late-stage SSc (p=0.017). No statistically significant differences were observed between early and late-stage SSc, concerning IL-2 expression among Th1 and Tc1 cells and IFN-γ expression among Th1 cells.
There were no significant association between disease subset, history of digital necrosis and internal organs’ involvement, mRSS or disease activity and the frequency of IL-2, TNF-α and IFN-γ expression among Th1 or Tc1 cells.
Conclusions The frequency of TNF-α-producing Tc1 cells was higher in late-stage SSc. The potential pathogenic relevance of these observations justifies further investigation, concerning the profile of proinflammatory cytokines and their potential involvement in different stages of the disease.
References Arthritis Rheum. 1992 Jan;35(1):67-72.
Disclosure of Interest None Declared
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